Department of Physiology, Dicle University, Faculty of Medicine Diyarbakır, Turkey.
Plant and Animal Production Department, Equine and Training Program, Vocational School of Veterinary Medicine, İstanbul University-Cerahpaşa, İstanbul, Turkey.
Acta Pharm. 2024 Mar 30;74(1):117-130. doi: 10.2478/acph-2024-0001. Print 2024 Mar 1.
Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg day doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg day reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg day, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg day, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg day, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg day dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg day is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.
他汀类药物治疗可能会增加患糖尿病的风险；目前关于他汀类药物如何影响葡萄糖调节和血糖控制的数据不足，他汀类药物对与碳水化合物代谢相关的肝酶的影响也尚未得到充分研究。因此，我们旨在比较他汀类药物衍生物普伐他汀和罗苏伐他汀在实验性糖尿病大鼠模型中对碳水化合物代谢的影响。使用雌性 Wistar 白化大鼠，通过腹腔注射链脲佐菌素诱导糖尿病。此后，将 10 和 20mg/kg 剂量的普伐他汀和罗苏伐他汀通过口服灌胃给予糖尿病大鼠，持续 8 周。在实验结束时，测量体重、空腹血糖、血清胰岛素、胰岛素抵抗（HOMA-IR）、肝糖原和与碳水化合物代谢相关的肝酶水平。两种剂量的普伐他汀均显著增加糖尿病大鼠的体重，而罗苏伐他汀，特别是 20mg/kg 剂量，显著降低体重。普伐他汀，特别是 20mg/kg 剂量，导致肝糖原合酶和葡萄糖 6-磷酸脱氢酶水平显著升高，但糖原磷酸化酶、乳酸脱氢酶和葡萄糖-6-磷酸酶水平显著降低。因此，普伐他汀部分改善了糖尿病引起的肝酶异常变化，特别是在 20mg/kg 剂量时，降低了空腹血糖水平并增加了肝糖原含量。然而，罗苏伐他汀，特别是在 20mg/kg 剂量时，显著降低了糖尿病大鼠的肝糖原合酶和丙酮酸激酶水平，但增加了糖原磷酸化酶水平。罗苏伐他汀，20mg/kg 剂量，导致糖尿病大鼠的体重和肝糖原含量显著下降。可以得出结论，普伐他汀，特别是 20mg/kg 剂量，通过调节碳水化合物代谢，更有效地改善糖尿病的负面影响。
